The ever increasing prevelance of bacteria harboring extrachromosomal elements or plasmids that confer resistance to chemotherapeutic drugs, that specify production of hemolysins, bacteriocins, toxins and other invasions, and/or that alter biochemical traits so as to make diagnosis difficult, is causing curtailment of bacterial infectious diseases to be increasingly more difficult and therefore constitutes a threat to the public health. The objective of our research is to study transmission and functions of plasmids in gram negative bacteria so as to be able to develop means for effective control and treatment of bacterial infectious diseases. Most of the research will be concerned with R factors in Escherichia coli and Salmonella typhimurium and will utilize minicell-producing strains of both of these bacterial species. During the coming year we will specifically investigate a) the genetic and biochemical nature of cell/cell interactions between donor and resipient strains leading to plasmid transfer, b) the mechanism of conjugal replication and transfer of plasmids, c) the nature of chromosomal control over plasmid vegetative replication and segregation, d) the nature of plasmid- specified messenger RNA and the regulation of its synthesis and e) the preparation of antibodies to plasmid-specified gene products and the efficacy of immunizing mice with such plasmid-specified gene products in providing protective immunity to plasmid-containing strains of bacteria. We will utilize the technologies of microbial genetics, molecular biology and immunology in this research.